Tocilizumab for the Treatment of Cytokine Release Syndrome in Patients With COVID-19 (SARS-CoV-2 Infection)

Tociluzumab for Cytokine Release Syndrome With SARS-CoV-2: An Open-Labeled, Randomized Phase 3 Trial

This phase III trial compares the effect of adding tocilizumab to standard of care versus standard of care alone in treating cytokine release syndrome (CRS) in patients with SARS-CoV-2 infection. CRS is a potentially serious disorder caused by the release of an excessive amount of substance that is made by cells of the immune system (cytokines) as a response to viral infection. Tocilizumab is used to decrease the body's immune response. Adding tocilizumab to standard of care may work better in treating CRS in patients with SARS-CoV-2 infection compared to standard of care alone.

Study Overview

• Status: Withdrawn
• Conditions: Coronary Artery Disease; Diabetes Mellitus; Chronic Obstructive Pulmonary Disease; Cerebrovascular Accident; Chronic Renal Failure; Malignant Neoplasm; SARS Coronavirus 2 Infection
• Intervention / Treatment: Biological: Tocilizumab; Other: Best Practice

Detailed Description

PRIMARY OBJECTIVE:

I. To decrease the length of invasive mechanical ventilation (MV) and rate of 30-day mortality from CRS due to SARS-CoV-2.

SECONDARY OBJECTIVES:

I. To decrease the rates of intensive care unit (ICU) transfer. II. To decrease the rate of invasive mechanical ventilation (MV). III. To decrease the length of ICU stay. IV. To decrease the rate of tracheostomy. V. Safety and efficacy of tociluzumab. VI. Biomarker assessment for response.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive tocilizumab intravenously (IV) every 12 hours for up to 3 doses in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care.

ARM II: Patients receive standard of care.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital/Winship Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis with SARS-CoV-2 by the currently available assays (Food and Drug Administration [FDA] approved)

• Should be hospitalized and exhibit at least one of the following predictors of mortality

  • Age >= 65 years
  • Current smoker (smoked >= 100 cigarettes in life and actively smoking)
  • Chronic obstructive pulmonary disease (COPD)
  • Diabetes
  • Hypertension
  • Coronary artery disease
  • Cerebrovascular accident (CVA)
  • Chronic renal disease (creatinine of >= 2 mg/dl)
  • Cancer
  • Patients that have C-reactive protein (CRP) >= 10 mg/L
  • D-dimer >= 0.5 mg/L
  • Procalcitonin >= 0.5 mg/L
  • Lactate dehydrogenase (LDH) >= upper limit of normal (ULN)
• Patients or authorized family member willing to sign informed consent to participate in this study

Exclusion Criteria:

• Pregnant or lactating women
• Hypersensitivity to tocilizumab
• Patients or authorized family member unwilling to sign informed consent to participate in this study
• Uncontrolled tuberculosis, or any uncontrolled fungal infection (eg: candidemia)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (tocilizumab, standard of care); Patients receive tocilizumab IV every 12 hours for up to 3 doses in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care.	Biological: Tocilizumab; Given IV; Other Names: RoActemra; Actemra; Immunoglobulin G1, Anti-(Human Interleukin 6 Receptor) (Human-Mouse Monoclonal MRA Heavy Chain), Disulfide with Human-Mouse Monoclonal MRA Kappa-Chain, Dimer; MRA; R-1569; Other: Best Practice; Receive standard of care; Other Names: standard of care; standard therapy
Active Comparator: Arm II (standard of care); Patients receive standard of care.	Other: Best Practice; Receive standard of care; Other Names: standard of care; standard therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
7-day length of invasive mechanical ventilation (MV)	The 7-day length of invasive MV for each arm will be estimated with 95% confidence intervals (CIs) using the exact binomial distribution. Their difference by the arms will be tested by Cochran-Mantel-Haenszel (CMH) test stratified by the age group and Sequential Organ Failure Assessment (SOFA) score at significance level of 0.05.	Up to 7 days
30-day mortality rate	Defined as death within 30-day after randomization. The 30-day mortality rate for each arm will be estimated with 95% CIs using the exact binomial distribution. Their difference by the arms will be tested CMH test stratified by the age group and SOFA score at significance level of 0.05.	Up to 30-day after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of intensive care (ICU) transfer	The rate of ICU transfer for each arm will be estimated with 95% CIs using the exact binomial distribution. Their difference by the arms will be tested CMH test stratified by the age group and SOFA score at significance level of 0.05.	Up to 2 years
Rate of invasive mechanical ventilation	The rate of invasive mechanical ventilation for each arm will be estimated with 95% CIs using the exact binomial distribution. Their difference by the arms will be tested CMH test stratified by the age group and SOFA score at significance level of 0.05.	Up to 2 years
Rate of tracheostomy	The rate of tracheostomy for each arm will be estimated with 95% CIs using the exact binomial distribution. Their difference by the arms will be tested CMH test stratified by the age group and SOFA score at significance level of 0.05.	Up to 2 years
Length of ICU stay	Will first be described by median and inter-quartile, and then compared between two arms by Wilcoxon Sum-Rank test	Up to 2 years
Length of hospital stay		Up 2 years

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Ajay K Nooka, Emory University Hospital/Winship Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2020
• Primary Completion (Actual): June 2, 2020
• Study Completion (Actual): June 2, 2020

Study Registration Dates

• First Submitted: April 7, 2020
• First Submitted That Met QC Criteria: April 22, 2020
• First Posted (Actual): April 24, 2020

Study Record Updates

• Last Update Posted (Actual): June 18, 2020
• Last Update Submitted That Met QC Criteria: June 16, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Kidney Diseases; Urologic Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Renal Insufficiency; Shock; Coronary Disease; Renal Insufficiency, Chronic; Stroke; Neoplasms; Coronary Artery Disease; COVID-19; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Infections; Kidney Failure, Chronic; Cytokine Release Syndrome; Physiological Effects of Drugs; Immunologic Factors; Immunoglobulins; Immunoglobulin G
• Other Study ID Numbers: STUDY00000419; P30CA138292 (U.S. NIH Grant/Contract); NCI-2020-02314 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); WINSHIP4998-20 (Other Identifier: Emory University Hospital/Winship Cancer Institute)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Results of the trial and not individual patient data will be shared. The study protocol, consent, and investigator's brochure will be available. The statistical plan is incorporated into the protocol, along with inclusion and exclusion criteria.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No